In spite of decades of great efforts, it is still very challenging to realize accurate design and synthesis of second-order nonlinear optical (NLO) crystals. KBe2BO3F2 (KBBF) is the sole NLO material that can output deep-ultraviolet light by direct second-harmonic generation process, so it is an ideal choice to use KBBF as the structural template to design environment-friendly candidates with better growth habit based on the reported compounds. In this review, we will elaborate the accurate design and synthesis of high-performance NLO materials from the perspective of microscopic crystal structure based on KBBF, hoping to provide deep understanding on how to rationally design and synthesize targeted compounds efficiently and quickly. In addition, according to multiple requirements on ultraviolet NLO crystals, including second-harmonic generation, cut-off edge, and birefringence, we propose a new concept so-called quality factor to comprehensively evaluate the overall performance of new ultraviolet NLO materials. This concept would help to directly and readily evaluate the ability of an ultraviolet NLO material to achieve practical NLO output.